The NIH Definition of Clinical Trial and its Implications: Part One of Two

Part One of this post explores how to determine if a study qualifies as a clinical trial under NIH’s definition. Part Two of this post will discuss NIH’s clinical trial requirements and will be published on Ampersand next weekSubscribe to Ampersand to receive a notification when Part Two goes live.

One of the most illuminating sessions from PRIM&R’s 2017 SBER Conference was “Clinical Trials in the SBER Context” by Melissa W. Riddle, PhD (Chief, Behavioral and Social Sciences Research Branch, National Institute of Dental and Craniofacial Research) and Cindy S. Shindledecker, CIP (Director, Health Sciences and Behavioral Sciences Institutional Review Board, University of Michigan). Dr. Riddle was absent, but her colleague Wendy Webber, ND, PhD, MPH (Acting Deputy Director, National Center for Complementary and Integrative Health) was able to do an impromptu presentation on behalf of NIH.

Though NIH’s revised definition of clinical trial has been in effect since 2014, IRBs are still struggling to interpret the definition. According to Dr. Webber, NIH’s intent was to create a broad definition, though she did offer guidance on how to interpret the definition by breaking down its various components.  

Here is NIH’s definition of clinical trial, for reference:

“A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.

According to the NIH, in order for a study to qualify as a clinical trial, the answers to the following four questions about the study must be “Yes.”

  • Does the study involve human participants?
    Essentially, only human subjects research can be classified as a clinical trial. Non human-subjects research (NHSR) studies cannot be clinical trials.
  • Are the participants prospectively assigned to an intervention?
    To be prospectively assigned, there need not be randomization or a control group; in fact, a single-arm study can meet the definition. But the study must enroll people into at least one arm and assign them to a procedure or task that they would not be doing if they weren’t in the research study. Evaluating a group’s impressions of a workshop that would take place regardless of the existence of the study would not be considered prospective assignment to an intervention; however, developing a workshop and putting it on in order to evaluate its effectiveness would qualify as prospective assignment to an intervention.
  • Is the study designed to evaluate the effect of the intervention on the participants?
    In order for a procedure to qualify as an intervention, it must involve manipulation of a subject or their environment for purposes of modifying one or more endpoints. Surveying or interviewing someone about their opinions alone does not involve a manipulation, and therefore would not qualify as an intervention. But assigning someone to do a workout and then surveying them about their thoughts on the workout would qualify as an intervention; the workout involves a manipulation of the participant’s behavior.
  • Is the effect being evaluated a health-related biomedical or behavioral outcome?
    Assigning participants to an intervention alone isn’t enough to tip the study into the clinical trial zone; the researchers must be studying the effect of the intervention on the participant’s health using biomedical or behavioral measures. For example, assigning someone to do a workout regimen over the course of a month, and measuring the change in their blood pressure over time (biomedical, health-related outcome) and their stress levels via survey measures (behavioral, health-related outcome) would qualify. But assigning someone to a workout regimen to test whether it helps them improve their score on a video game would be an intervention without a health-related outcome, and would therefore not be a clinical trial.

Currently, the clinical trial definition and its implications (which I cover in Part Two of this post) only apply to NIH-funded studies. Therefore, I would add a fifth criteria to the four questions suggested by NIH:

  • Is the study NIH-funded?

And since funding drives this definition, I would ask this question before considering any of the others. If a study is NIH-funded, then it is worth finding out if it meets the NIH definition of clinical trial. If the study is not NIH-funded (even if it is funded by a different federal agency), I would stop right there. No NIH funding? Not a clinical trial (for the purposes of this evaluation).

There is some talk that the other federal agencies will eventually jump on the bandwagon. But until they do, I would suggest IRBs apply the NIH definition of clinical trial as narrowly as possible, to avoid being on the hook for NIH’s clinical trial requirements (to come in Part Two.)

Sarah Luery is an IRB Administrator at the University of Southern California and a member of the 2017 SBER and AER Conference Blog Squad.

Members of PRIM&R’s Blog Squad and other guest contributors are valued members of our community willing to share their insights. The views expressed in their posts do not necessarily reflect those of PRIM&R or its employees.

Save the date for PRIM&R’s 2018 Advancing Ethical Research Conference, taking place November 14-17 in San Diego, CA.